On December 18, 2024 Iambic Therapeutics, a clinical-stage biotechnology company developing novel therapeutics using its unique AI-driven discovery platform, reported that Tom Miller, Ph.D., Iambic’s Chief Executive Officer and Co-Founder, will present at the 43rd Annual JP Morgan Healthcare Conference (Press release, Iambic Therapeutics, DEC 18, 2024, View Source [SID1234649206]). The presentation will take place on Tuesday, January 14th, at 5 p.m. PT at the Westin St. Francis Hotel in San Francisco.

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Dr. Miller will detail progress and anticipated milestones for Iambic’s emerging pipeline of development candidates, as well as advances to its AI drug discovery platform. The Company’s pipeline currently includes IAM1363, a highly selective, brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1/1b study, as well as a potential first-in-class selective dual CDK2/4 inhibitor for multiple cancer indications, an allosteric inhibitor for KIF18A, and additional new programs.

On December 17, 2024 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported the Independent Data Monitoring Committee (IDMC) recommendation of a move-forward dose and the completion of the Part 2a dose optimization consistent with the U.S. Food and Drug Administration’s (FDA) Project Optimus guidelines for the potential registration-enabling Phase 2/3 trial evaluating the combination of darovasertib and crizotinib in the first-line (1L) setting in patients with HLA-A2-negative (HLA-A2(-)) metastatic uveal melanoma (MUM) (Press release, Ideaya Biosciences, DEC 17, 2024, View Source [SID1234649173]).

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"We are pleased with the recommendation of the IDMC and the selection of the move-forward dose for our potential registration-enabling trial evaluating the darovasertib and crizotinib combination in first-line HLA-A2(-) MUM patients. This allows us to complete the Part 2a portion of the study and seamlessly continue to enroll in Part 2b towards a potential accelerated approval based on the primary endpoint of median progression free survival," said Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

"The combination of darovasertib and crizotinib as first-line treatment has shown compelling preliminary clinical results in patients with HLA-A2(-) MUM. The IDMC recommendation of the move-forward dose supports the advancement of this potentially registration-enabling Phase 2/3 trial and is an important step in bringing a new treatment option to patients with MUM. Additionally, the continued rapid enrollment further validates the strong interest from physicians and patients, and highlights the significant unmet need in these patients, who historically have faced a poor prognosis," added Meredith McKean, M.D., MPH, Director, Melanoma and Skin Cancer Research at Sarah Cannon Research Institute, and clinical investigator on the potential registration-enabling clinical trial.

The darovasertib and crizotinib combination in MUM has FDA Fast Track designation and is currently being evaluated in two clinical trials: a potentially registration-enabling Phase 2/3 trial of darovasertib and crizotinib combination in first-line HLA-A2(-) MUM (NCT05987332) and a Phase 2 trial (NCT03947385). Additionally, darovasertib as neoadjuvant monotherapy is currently being evaluated in a Phase 2 trial in primary uveal melanoma (NCT05907954). IDEAYA is also finalizing a clinical trial protocol and is targeting to initiate a potential Phase 3 registration-enabling study for neoadjuvant uveal melanoma patients in the first half of 2025.

On December 17, 2024 ESSA Pharma Inc. ("ESSA," or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company that, prior to the discontinuation of its clinical trials and preclinical and other development programs, has been focused on developing novel therapies for the treatment of prostate cancer, reported a corporate update and provided financial results for the fourth quarter and fiscal year ended September 30, 2024 (Press release, ESSA, DEC 17, 2024, View Source [SID1234649174]).

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"We recently made the difficult decision to terminate the clinical development of masofaniten, and withdraw the related IND and CTAs, based on an interim analysis of the data from the Phase 2 combination study, concluding that masofaniten combined with enzalutamide was unlikely to meet its primary endpoint," said David Parkinson, MD, President and CEO of ESSA. "We are currently evaluating and reviewing our strategic options focused on maximizing shareholder value and look forward to providing further updates in the near future."

Fourth Quarter Fiscal 2024 and Recent Updates

In October 2024, ESSA made the decision to terminate all clinical trials evaluating masofaniten and to withdraw the related IND and CTAs. The decision was based on the outcome of a futility analysis conducted as part of a protocol-specified interim review of the Phase 2 clinical trial evaluating masofaniten combined with enzalutamide versus enzalutamide monotherapy in patients with metastatic castration-resistant prostate cancer ("mCRPC") naïve to second-generation antiandrogens.

The interim analysis, which reviewed the Phase 2 safety, PK and efficacy data, showed that the study enzalutamide monotherapy control arm (which is the standard of care for this patient population) had a much higher rate of PSA90 response than was expected based upon historical data. In addition, there was no clear efficacy benefit seen with the combination of masofaniten plus enzalutamide compared to enzalutamide single agent. A futility analysis determined a low likelihood of meeting the prespecified primary endpoint of the study. It was therefore concluded that the study was unlikely to achieve its primary endpoint.

The combination of masofaniten plus enzalutamide was well-tolerated with no new safety signals and a safety profile similar to that seen in Phase 1 monotherapy and combination studies.

ESSA has initiated a comprehensive process to explore and review a range of strategic options focused on maximizing shareholder value, which may include, but are not limited to a merger, amalgamation, take-over, business combination, asset sale or acquisition, shareholder distribution, wind-up, liquidation and dissolution, seek new products for development, or other strategic direction. The process is expected to involve headcount and other cost reductions.

On December 12, 2024, ESSA provided a notice of termination of the License Agreement to the Licensors, notifying the Licensors that it terminated the License Agreement in accordance with its terms, effective as of December 12, 2024.
Summary Financial Results
(Amounts expressed in U.S. dollars)

Net Loss. ESSA recorded a net loss of $28.5 million for the year ended September 30, 2024 compared to a net loss of $26.6 million for the year ended September 30, 2023. For the year ended September 30, 2024, this included non-cash share-based payments of $6.5 million compared to $5.3 million for the prior year, recognized for stock options granted and vesting. Net loss for the fourth quarter ended September 30, 2024 was $6.4 million compared to a net loss of $5.5 million for the fourth quarter ended September 30, 2023.
Research and Development ("R&D") expenditures. R&D expenditures for the year ended September 30, 2024 were $21.2 million compared to $21.3 million for the year ended September 30, 2023, and include non-cash costs related to share-based payments ($1.8 million for the year ended 2024 compared to $2.7 million for the year ended 2023). R&D expenditures for the fourth quarter ended September 30, 2024 were $4.2 million compared to $5.2 million for the fourth quarter ended September 30, 2023 due to lower expenditures on preclinical and manufacturing.
General and Administration ("G&A") expenditures. G&A expenditures for the year ended September 30, 2024 were $13.2 million compared to $10.8 million for the year ended September 30, 2023, and include non-cash costs related to share-based payments of $4.7 million for the year ended 2024 compared to $2.6 million for the year ended 2023. G&A expenditures for the fourth quarter ended September 30, 2024 were $3.5 million compared to $1.9 million for the fourth quarter ended September 30, 2023. The increase for the fourth quarter was primarily due to increased share-based payments and higher salary figures.
Liquidity and Outstanding Share Capital

As of September 30, 2024, the Company had available cash reserves and short-term investments of $126.8 million and net working capital of $124.3 million. The Company has no long-term debt facilities.
As of September 30, 2024, the Company had 44,388,550 common shares issued and outstanding, and there were 2,920,000 common shares issuable upon the exercise of prefunded warrants at an exercise price of $0.0001.

On December 17, 2024 AB Science SA (Euronext – FR0010557264 – AB) reported an update on its AB8939 program in acute myeloid leukemia (AML) (Press release, AB Science, DEC 17, 2024, View Source [SID1234649151]).

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AB8939 target product profile

AB8939 is a next generation synthetic microtubule destabilizer and stem cell targeted ALDH1/2 inhibitor with key differentiating factors for treatment of refractory/relapsing acute myeloid leukemia (AML).

▪AB8939 blocks proliferating leukemia cells through microtubules AB8939 destabilizes microtubule, is not subjected to multidrug resistance as it does not bind to PgP, responsible of efflux outside the cells and AB8939 is not degraded by the enzyme myeloperoxidase.

▪AB8939 targets leukemia cancer stem cells though inhibition of ALDH AB8939 inhibits ALDH1/2 and favors the bone marrow repopulation of normal progenitors. ▪AB8939 is well suited for the treatment of relapsed or refractory AML AB8939 has activity seen across refractory AML cell lines, has an additive effect with referenced first line treatment for AML, namely cytarabine, azacitidine and venetoclax.

▪AB8939 has a potential use in AML with MECOM AB8939 has shown a signal of efficacy in AML with MECOM gene rearrangement, a subset of patients that show extreme resistance to chemotherapies and exhibit the worst survival prognosis

▪AB8939 shows absence of hematological toxicity based on clinical data

Addressable market with AB8939 in relapsed/refractory AML

Treatments in relapsed or refractory AML represent an estimated market size potential above EUR 2 billion per annum.

Non clinical pharmacology

Animal experiments have shown the following properties for AB8939 relevant for the treatment of AML: ▪AB8939 is active against chemotherapy naive or chemotherapy refractory/relapsing patient’s AML cancers cells ex vivo ▪AB8939 eradicates blasts in Blood and Bone Marrow in 5-AraC-resistant (Cytarabine) PDX

▪AB8939 increases survival and has an additive effect in combination with reference treatment Azacitidine and Venetoclax

▪ALDHs expression is a hallmark of cancer stem cells (CSCs) and AB8939 is an inhibitor of ALDH1/2. Therefore, AB8939 is a targeted therapy for leukemia cancer stem cells

▪AB8939 eradicates Leukemia Cancer Stem Cells in a human PDX AML model

Phase 1 preliminary safety

The objective of the phase 1 is to determine the maximum tolerated dose (MTD) for three different cycles of AB8939. The first step of the phase 1 has been completed with 28 patients enrolled, evaluating the maximum tolerated dose after 3 consecutive days of AB8939 treatment. The second step of the phase 1 is close to completion and enrolled 10 patients, evaluating the maximum tolerated dose after 10 consecutive days of AB8939 treatment. The next step is to evaluate the maximum tolerated dose after 14 consecutive days of AB8939 treatment in combination with venetoclax or azacitidine and in combination with venetoclax plus azacitidine, both drugs being widely used on AML and for which AB8939 has shown an additive effect.

Preliminary activity in MECOM

MECOM is associated with a dismal outcome, with almost all patients dying within 12 months after relapse. AB8939 is a stem cell ALDH targeted therapy with potential use in AML with MECOM.

▪ALDH gene expression is a marker of survival prognosis in AML. The higher the expression, the worse the prognosis

▪MECOM is associated with the worst prognosis in AML

▪MECOM is a rearrangement or a mutation of the chromosome 3 locus Q26 that codes for the transcription factor gene EVI1 (Ecotropic virus integration site-1)

▪The expression of ALDH1A1 is regulated by EVI1 and has an outstanding role in the formation and transformation of hematopoietic cells and in particular leukemia stem cells

▪The hypothesis is that in MECOM, the rearrangement of chromosome 3 Q26 leads to EVI1 over-expressing ALDH1A and induces high resistance of leukemia stem cells, and AB8939 should have an impact on leukaemia stem cells by inhibiting ALDH1 AB8939 has shown activity on MECOM rearrangement, based on non-clinical data and early clinical data in relapsing/refractory line of treatment, with 50% response rate observed. Planned phases 2 The next steps in the clinical development will be discussed with FDA and EMA. The first intended step is to develop AB8939 in patients with MECOM AML, through a single arm study with less than 60 patients supporting an accelerated approval based on response rate.

The second objective is to position AB8939 in broader forms of AML and position AB8939 in relapsed or refractory AML. The third objective is to capture the full market potential of AB8939 and position AB8939 in first line in combination with standard of care.

Intellectual property

AB8939 intellectual property rights in AML are secured until 2036 through a ‘composition of matter’ patent and potentially until 2044 in AML with chromosome abnormality, including MECOM, through a ‘second medical use’ patent. AB Science is the sole proprietary holder of AB8939 and its family of compounds.

On December 17, 2024 Sairopa B.V., reported it has achieved a milestone event in its exclusive clinical development and option agreement with Exelixis, Inc. (Nasdaq: EXEL) involving ADU-1805, an innovative anti-SIRPα antibody with the potential to enhance the immune system’s ability to combat cancer (Press release, Sairopa, DEC 17, 2024, View Source [SID1234649153]).

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Under the terms of the agreement, Exelixis has an exclusive option to license worldwide development and commercialization rights for ADU-1805 and other anti-SIRPα antibodies following the review of data from Sairopa’s phase 1 clinical studies. As part of its collaboration with Exelixis, Sairopa has previously received from Exelixis an upfront payment of $40 million, a $35 million milestone payment upon Investigational New Drug (IND) clearance of ADU-1805 with the U.S. Food and Drug Administration, and $35 million in milestone payments linked to advances within the clinical development of ADU-1805, in monotherapy as well as in combination with a PD-1 inhibitor.

"Today’s operational update signifies a step forward in the partnered effort to develop next-generation therapies for cancer patients worldwide," said Gurvinder S. Chahal, Chief Business Officer of Sairopa. "The advances seen within our clinical program are a testament to the diligent work and innovative science behind our partnership with Exelixis, bringing us closer to realizing our mission of modulating the immune system to improve outcomes for cancer patients."

The safety and pharmacokinetics of ADU-1805 are currently being evaluated in a first-in-human, open-label, multicenter, multi-arm phase 1 study. To date, patients have been enrolled across the U.S. and several European countries, with assessments ongoing in both the ADU-1805 monotherapy and the ADU-1805 plus pembrolizumab dose escalation arms.

This collaboration combines Exelixis’ proven track record in oncology drug development and commercialization with Sairopa’s expertise in generating innovative cancer immunotherapies, setting the stage for potentially transformative treatments in oncology.